JP2010521458A5

JP2010521458A5 -

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Publication number: JP2010521458A5
Authority: JP; Japan
Prior art keywords: group; trifluoromethyl; ylamino; pyridin; compound
Prior art date: 2008-03-10
Legal status : Granted

Application number

JP2009553600A

Other languages

English (en)

Japanese (ja)

Other versions

JP5569956B2 (ja

JP2010521458A (ja

Filing date

2008-03-10

Publication date

2011-05-06

2008-03-10 Application filed filed Critical

2008-03-10 Priority claimed from PCT/US2008/003205 external-priority patent/WO2008115369A2/fr

2010-06-24 Publication of JP2010521458A publication Critical patent/JP2010521458A/ja

2011-05-06 Publication of JP2010521458A5 publication Critical patent/JP2010521458A5/ja

2014-08-13 Application granted granted Critical

2014-08-13 Publication of JP5569956B2 publication Critical patent/JP5569956B2/ja

Status Expired - Fee Related legal-status Critical Current

2028-03-10 Anticipated expiration legal-status Critical

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150000001875 compounds Chemical class 0.000 claims description 251
-1 cyano, thio, nitro Chemical group 0.000 claims description 205
239000000203 mixture Substances 0.000 claims description 118
KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 77
125000000217 alkyl group Chemical group 0.000 claims description 57
125000003118 aryl group Chemical group 0.000 claims description 40
102000001253 Protein Kinases Human genes 0.000 claims description 37
125000001072 heteroaryl group Chemical group 0.000 claims description 37
JUJWROOIHBZHMG-UHFFFAOYSA-N pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 35
125000005842 heteroatoms Chemical group 0.000 claims description 33
229910052799 carbon Inorganic materials 0.000 claims description 31
125000005843 halogen group Chemical group 0.000 claims description 29
229910052717 sulfur Inorganic materials 0.000 claims description 29
229910052739 hydrogen Inorganic materials 0.000 claims description 28
239000001257 hydrogen Substances 0.000 claims description 28
125000001424 substituent group Chemical group 0.000 claims description 27
125000000623 heterocyclic group Chemical group 0.000 claims description 26
230000002401 inhibitory effect Effects 0.000 claims description 26
125000003545 alkoxy group Chemical group 0.000 claims description 25
108060006633 Protein Kinases Proteins 0.000 claims description 21
230000000694 effects Effects 0.000 claims description 21
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 21
238000000034 method Methods 0.000 claims description 19
125000002950 monocyclic group Chemical group 0.000 claims description 19
229910052757 nitrogen Inorganic materials 0.000 claims description 18
241000124008 Mammalia Species 0.000 claims description 17
108091000081 Phosphotransferases Proteins 0.000 claims description 17
VEXZGXHMUGYJMC-UHFFFAOYSA-N HCl Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 16
125000004122 cyclic group Chemical group 0.000 claims description 16
229910052760 oxygen Inorganic materials 0.000 claims description 16
125000000753 cycloalkyl group Chemical group 0.000 claims description 15
201000010099 disease Diseases 0.000 claims description 15
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 15
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 15
239000002253 acid Substances 0.000 claims description 14
201000011510 cancer Diseases 0.000 claims description 14
125000004093 cyano group Chemical group *C#N 0.000 claims description 14
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 14
XSQUKJJJFZCRTK-UHFFFAOYSA-N urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims description 13
210000001650 Focal Adhesions Anatomy 0.000 claims description 12
125000003342 alkenyl group Chemical group 0.000 claims description 12
230000003211 malignant Effects 0.000 claims description 11
LRHPLDYGYMQRHN-UHFFFAOYSA-N n-butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 claims description 11
239000000651 prodrug Substances 0.000 claims description 11
229940002612 prodrugs Drugs 0.000 claims description 11
239000000126 substance Substances 0.000 claims description 11
RAXXELZNTBOGNW-UHFFFAOYSA-N Imidazole Chemical compound C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 10
125000000304 alkynyl group Chemical group 0.000 claims description 10
238000001914 filtration Methods 0.000 claims description 10
SIKJAQJRHWYJAI-UHFFFAOYSA-N indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 claims description 10
239000011780 sodium chloride Substances 0.000 claims description 10
125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 9
230000027455 binding Effects 0.000 claims description 9
239000003446 ligand Substances 0.000 claims description 9
125000001309 chloro group Chemical group Cl* 0.000 claims description 8
125000004435 hydrogen atoms Chemical group [H]* 0.000 claims description 8
125000004043 oxo group Chemical group O=* 0.000 claims description 8
150000003839 salts Chemical class 0.000 claims description 8
ZWRMSOMIVOVMQX-UHFFFAOYSA-M 2-(2-aminoethyldisulfanyl)ethanamine;palladium(2+);chloride Chemical compound [Cl-].[Pd+2].NCCSSCCN ZWRMSOMIVOVMQX-UHFFFAOYSA-M 0.000 claims description 7
230000002159 abnormal effect Effects 0.000 claims description 7
125000002619 bicyclic group Chemical group 0.000 claims description 7
XYFCBTPGUUZFHI-UHFFFAOYSA-N phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 claims description 7
229910000073 phosphorus hydride Inorganic materials 0.000 claims description 7
PBMFSQRYOILNGV-UHFFFAOYSA-N Pyridazine Chemical compound C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 claims description 6
239000004202 carbamide Substances 0.000 claims description 6
238000004519 manufacturing process Methods 0.000 claims description 6
239000012453 solvate Substances 0.000 claims description 6
229910052723 transition metal Inorganic materials 0.000 claims description 6
150000003624 transition metals Chemical class 0.000 claims description 6
CZPWVGJYEJSRLH-UHFFFAOYSA-N 289-95-2 Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims description 5
125000001246 bromo group Chemical group Br* 0.000 claims description 5
125000004663 dialkyl amino group Chemical group 0.000 claims description 5
238000000338 in vitro Methods 0.000 claims description 5
PXZQEOJJUGGUIB-UHFFFAOYSA-N isoindolin-1-one Chemical compound C1=CC=C2C(=O)NCC2=C1 PXZQEOJJUGGUIB-UHFFFAOYSA-N 0.000 claims description 5
ZCQWOFVYLHDMMC-UHFFFAOYSA-N oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 claims description 5
KYQCOXFCLRTKLS-UHFFFAOYSA-N pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 claims description 5
WTKZEGDFNFYCGP-UHFFFAOYSA-N pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 claims description 5
FZWLAAWBMGSTSO-UHFFFAOYSA-N thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 claims description 5
BSUNTQCMCCQSQH-UHFFFAOYSA-N triazine Chemical compound C1=CN=NN=C1.C1=CN=NN=C1 BSUNTQCMCCQSQH-UHFFFAOYSA-N 0.000 claims description 5
150000003852 triazoles Chemical class 0.000 claims description 5
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 4
125000003282 alkyl amino group Chemical group 0.000 claims description 4
125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims description 4
125000004433 nitrogen atoms Chemical group N* 0.000 claims description 4
239000008194 pharmaceutical composition Substances 0.000 claims description 4
125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 3
102000016621 Focal Adhesion Protein-Tyrosine Kinases Human genes 0.000 claims description 3
108010067715 Focal Adhesion Protein-Tyrosine Kinases Proteins 0.000 claims description 3
125000002618 bicyclic heterocycle group Chemical group 0.000 claims description 3
125000006728 (C1-C6) alkynyl group Chemical group 0.000 claims description 2
125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims description 2
125000001153 fluoro group Chemical group F* 0.000 claims description 2
125000002768 hydroxyalkyl group Chemical group 0.000 claims description 2
230000036210 malignancy Effects 0.000 claims description 2
102000030951 Phosphotransferases Human genes 0.000 claims 1
239000003795 chemical substances by application Substances 0.000 claims 1
DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 105
IAZDPXIOMUYVGZ-UHFFFAOYSA-N dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 102
XEKOWRVHYACXOJ-UHFFFAOYSA-N acetic acid ethyl ester Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 77
OKKJLVBELUTLKV-UHFFFAOYSA-N methanol Chemical group OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 71
239000007787 solid Substances 0.000 description 71
238000005160 1H NMR spectroscopy Methods 0.000 description 61
XKRFYHLGVUSROY-UHFFFAOYSA-N argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 42
239000002904 solvent Substances 0.000 description 37
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 36
239000000243 solution Substances 0.000 description 36
239000012043 crude product Substances 0.000 description 35
102100017873 PTK2 Human genes 0.000 description 34
235000019439 ethyl acetate Nutrition 0.000 description 34
FJDQFPXHSGXQBY-UHFFFAOYSA-L Caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 33
238000010898 silica gel chromatography Methods 0.000 description 32
239000000047 product Substances 0.000 description 31
238000006243 chemical reaction Methods 0.000 description 30
238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 30
VYPSYNLAJGMNEJ-UHFFFAOYSA-N silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 29
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 25
125000004432 carbon atoms Chemical group C* 0.000 description 24
YMWUJEATGCHHMB-UHFFFAOYSA-N methylene dichloride Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 24
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 23
CXNIUSPIQKWYAI-UHFFFAOYSA-N Xantphos Chemical compound C=12OC3=C(P(C=4C=CC=CC=4)C=4C=CC=CC=4)C=CC=C3C(C)(C)C2=CC=CC=1P(C=1C=CC=CC=1)C1=CC=CC=C1 CXNIUSPIQKWYAI-UHFFFAOYSA-N 0.000 description 22
UIIMBOGNXHQVGW-UHFFFAOYSA-M buffer Substances [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 22
UFHFLCQGNIYNRP-UHFFFAOYSA-N hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 22
229910052786 argon Inorganic materials 0.000 description 21
WEVYAHXRMPXWCK-UHFFFAOYSA-N acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 16
150000003840 hydrochlorides Chemical class 0.000 description 16
239000000969 carrier Substances 0.000 description 15
238000002953 preparative HPLC Methods 0.000 description 15
125000003277 amino group Chemical group 0.000 description 14
VLKZOEOYAKHREP-UHFFFAOYSA-N hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 14
238000004166 bioassay Methods 0.000 description 13
LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 12
BLDAPDVJFOJWMZ-UHFFFAOYSA-N 2-[[2-chloro-5-(trifluoromethyl)pyridin-4-yl]amino]-N-methylbenzamide Chemical compound CNC(=O)C1=CC=CC=C1NC1=CC(Cl)=NC=C1C(F)(F)F BLDAPDVJFOJWMZ-UHFFFAOYSA-N 0.000 description 12
210000004027 cells Anatomy 0.000 description 12
LFQSCWFLJHTTHZ-UHFFFAOYSA-N ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 12
XEEQBBXEZSNIQV-UHFFFAOYSA-N 2-chloro-4-iodo-5-(trifluoromethyl)pyridine Chemical compound FC(F)(F)C1=CN=C(Cl)C=C1I XEEQBBXEZSNIQV-UHFFFAOYSA-N 0.000 description 11
PAYRUJLWNCNPSJ-UHFFFAOYSA-N aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 11
OKTJSMMVPCPJKN-UHFFFAOYSA-N carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 11
229910052763 palladium Inorganic materials 0.000 description 11
125000004429 atoms Chemical group 0.000 description 10
NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 10
239000011541 reaction mixture Substances 0.000 description 10
JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 9
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 9
239000000460 chlorine Substances 0.000 description 9
238000002347 injection Methods 0.000 description 9
239000007924 injection Substances 0.000 description 9
NQMRYBIKMRVZLB-UHFFFAOYSA-N methylamine hydrochloride Chemical compound [Cl-].[NH3+]C NQMRYBIKMRVZLB-UHFFFAOYSA-N 0.000 description 9
239000003039 volatile agent Substances 0.000 description 9
239000003085 diluting agent Substances 0.000 description 8
239000002552 dosage form Substances 0.000 description 8
238000009472 formulation Methods 0.000 description 8
239000008079 hexane Substances 0.000 description 8
239000003921 oil Substances 0.000 description 8
235000019198 oils Nutrition 0.000 description 8
125000004149 thio group Chemical group *S* 0.000 description 8
OEBXWWBYZJNKRK-UHFFFAOYSA-N 1-methyl-2,3,4,6,7,8-hexahydropyrimido[1,2-a]pyrimidine Chemical compound C1CCN=C2N(C)CCCN21 OEBXWWBYZJNKRK-UHFFFAOYSA-N 0.000 description 7
BQTMHUUWYHEPNQ-UHFFFAOYSA-N 2-methoxy-4-morpholin-4-ylaniline Chemical compound C1=C(N)C(OC)=CC(N2CCOCC2)=C1 BQTMHUUWYHEPNQ-UHFFFAOYSA-N 0.000 description 7
150000001412 amines Chemical class 0.000 description 7
235000014113 dietary fatty acids Nutrition 0.000 description 7
239000000194 fatty acid Substances 0.000 description 7
239000003999 initiator Substances 0.000 description 7
239000000843 powder Substances 0.000 description 7
239000011734 sodium Substances 0.000 description 7
ZCHPKWUIAASXPV-UHFFFAOYSA-N acetic acid;methanol Chemical compound OC.CC(O)=O ZCHPKWUIAASXPV-UHFFFAOYSA-N 0.000 description 6
150000001502 aryl halides Chemical class 0.000 description 6
239000002775 capsule Substances 0.000 description 6
239000003054 catalyst Substances 0.000 description 6
229910052801 chlorine Inorganic materials 0.000 description 6
125000000392 cycloalkenyl group Chemical group 0.000 description 6
239000003814 drug Substances 0.000 description 6
125000001041 indolyl group Chemical group 0.000 description 6
229910052740 iodine Inorganic materials 0.000 description 6
239000000463 material Substances 0.000 description 6
239000012044 organic layer Substances 0.000 description 6
230000003647 oxidation Effects 0.000 description 6
238000007254 oxidation reaction Methods 0.000 description 6
239000000725 suspension Substances 0.000 description 6
239000003826 tablet Substances 0.000 description 6
WYURNTSHIVDZCO-UHFFFAOYSA-N tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 6
0 **Nc1cc(N*)ncc1* Chemical compound **Nc1cc(N*)ncc1* 0.000 description 5
FBBFBZJZXFGFCK-UHFFFAOYSA-N 2-[[2-chloro-5-(trifluoromethyl)pyridin-4-yl]amino]-N-methylbenzenesulfonamide Chemical compound CNS(=O)(=O)C1=CC=CC=C1NC1=CC(Cl)=NC=C1C(F)(F)F FBBFBZJZXFGFCK-UHFFFAOYSA-N 0.000 description 5
206010061289 Metastatic neoplasm Diseases 0.000 description 5
241001465754 Metazoa Species 0.000 description 5
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 5
150000004665 fatty acids Chemical class 0.000 description 5
239000003112 inhibitor Substances 0.000 description 5
102000006495 integrins Human genes 0.000 description 5
108010044426 integrins Proteins 0.000 description 5
230000001394 metastastic Effects 0.000 description 5
238000002360 preparation method Methods 0.000 description 5
230000002829 reduced Effects 0.000 description 5
NINIDFKCEFEMDL-UHFFFAOYSA-N sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 5
239000011593 sulfur Substances 0.000 description 5
125000000335 thiazolyl group Chemical group 0.000 description 5
RFFLAFLAYFXFSW-UHFFFAOYSA-N 1,2-Dichlorobenzene Chemical compound ClC1=CC=CC=C1Cl RFFLAFLAYFXFSW-UHFFFAOYSA-N 0.000 description 4
HMYXHQDSYJOVBG-UHFFFAOYSA-N 2-chloro-N-(2-pyrimidin-2-ylphenyl)-5-(trifluoromethyl)pyridin-4-amine Chemical compound FC(F)(F)C1=CN=C(Cl)C=C1NC1=CC=CC=C1C1=NC=CC=N1 HMYXHQDSYJOVBG-UHFFFAOYSA-N 0.000 description 4
CCFGTKQIRWHYTB-UHFFFAOYSA-N 2-methyl-3-nitropyridine Chemical compound CC1=NC=CC=C1[N+]([O-])=O CCFGTKQIRWHYTB-UHFFFAOYSA-N 0.000 description 4
210000002744 Extracellular Matrix Anatomy 0.000 description 4
IQEKCKQBCMCLQF-UHFFFAOYSA-N N,N-dimethyl-2-(5-nitro-1H-indol-3-yl)-2-oxoacetamide Chemical compound C1=C([N+]([O-])=O)C=C2C(C(=O)C(=O)N(C)C)=CNC2=C1 IQEKCKQBCMCLQF-UHFFFAOYSA-N 0.000 description 4
238000007792 addition Methods 0.000 description 4
238000005859 coupling reaction Methods 0.000 description 4
RTZKZFJDLAIYFH-UHFFFAOYSA-N diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
229940079593 drugs Drugs 0.000 description 4
230000002255 enzymatic Effects 0.000 description 4
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 4
125000005241 heteroarylamino group Chemical group 0.000 description 4
229910000041 hydrogen chloride Inorganic materials 0.000 description 4
239000011630 iodine Substances 0.000 description 4
PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 4
XEEYBQQBJWHFJM-UHFFFAOYSA-N iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 4
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 4
CSNNHWWHGAXBCP-UHFFFAOYSA-L mgso4 Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 4
125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 4
125000002971 oxazolyl group Chemical group 0.000 description 4
125000004430 oxygen atoms Chemical group O* 0.000 description 4
125000003367 polycyclic group Chemical group 0.000 description 4
125000003226 pyrazolyl group Chemical group 0.000 description 4
125000004076 pyridyl group Chemical group 0.000 description 4
125000003107 substituted aryl group Chemical group 0.000 description 4
YXFVVABEGXRONW-UHFFFAOYSA-N toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 4
125000001425 triazolyl group Chemical group 0.000 description 4
ZMANZCXQSJIPKH-UHFFFAOYSA-N triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 4
KPWJZRQNNFFNJZ-UHFFFAOYSA-N 2-N-(2-methoxy-4-morpholin-4-ylphenyl)-4-N-(2-pyrimidin-2-ylphenyl)-5-(trifluoromethyl)pyridine-2,4-diamine Chemical compound COC1=CC(N2CCOCC2)=CC=C1NC(N=CC=1C(F)(F)F)=CC=1NC1=CC=CC=C1C1=NC=CC=N1 KPWJZRQNNFFNJZ-UHFFFAOYSA-N 0.000 description 3
WQYDASORCSDVNY-UHFFFAOYSA-N 2-[[5-bromo-2-(2-methoxy-4-morpholin-4-ylanilino)pyridin-4-yl]amino]-N-methylbenzamide Chemical compound CNC(=O)C1=CC=CC=C1NC1=CC(NC=2C(=CC(=CC=2)N2CCOCC2)OC)=NC=C1Br WQYDASORCSDVNY-UHFFFAOYSA-N 0.000 description 3
SVIILPGBQTUQPJ-UHFFFAOYSA-N 2-[[5-chloro-2-(2-methoxy-4-morpholin-4-ylanilino)pyridin-4-yl]amino]-N-methylbenzamide Chemical compound CNC(=O)C1=CC=CC=C1NC1=CC(NC=2C(=CC(=CC=2)N2CCOCC2)OC)=NC=C1Cl SVIILPGBQTUQPJ-UHFFFAOYSA-N 0.000 description 3
JMHVADDHAXZSPT-UHFFFAOYSA-N 2-[[5-cyano-2-(2-methoxy-4-morpholin-4-ylanilino)pyridin-4-yl]amino]-N-methylbenzamide Chemical compound CNC(=O)C1=CC=CC=C1NC1=CC(NC=2C(=CC(=CC=2)N2CCOCC2)OC)=NC=C1C#N JMHVADDHAXZSPT-UHFFFAOYSA-N 0.000 description 3
PMPFLCSHKNHZTF-UHFFFAOYSA-N 2-chloro-N-pyridin-2-yl-5-(trifluoromethyl)pyridin-4-amine Chemical compound FC(F)(F)C1=CN=C(Cl)C=C1NC1=CC=CC=N1 PMPFLCSHKNHZTF-UHFFFAOYSA-N 0.000 description 3
CCZWSTFVHJPCEM-UHFFFAOYSA-N 2-iodopyridine Chemical compound IC1=CC=CC=N1 CCZWSTFVHJPCEM-UHFFFAOYSA-N 0.000 description 3
CUYKNJBYIJFRCU-UHFFFAOYSA-N 3-Aminopyridine Chemical compound NC1=CC=CN=C1 CUYKNJBYIJFRCU-UHFFFAOYSA-N 0.000 description 3
JDBLLRTTXAUMAF-UHFFFAOYSA-N 4,5-difluoro-2-[[2-(2-methoxy-4-morpholin-4-ylanilino)-5-(trifluoromethyl)pyridin-4-yl]amino]-N-methylbenzamide Chemical compound CNC(=O)C1=CC(F)=C(F)C=C1NC1=CC(NC=2C(=CC(=CC=2)N2CCOCC2)OC)=NC=C1C(F)(F)F JDBLLRTTXAUMAF-UHFFFAOYSA-N 0.000 description 3
YMXOMWAFFGHJFC-UHFFFAOYSA-N 4-(3-methoxy-4-nitrophenyl)morpholine Chemical compound C1=C([N+]([O-])=O)C(OC)=CC(N2CCOCC2)=C1 YMXOMWAFFGHJFC-UHFFFAOYSA-N 0.000 description 3
GUBGYTABKSRVRQ-UUNJERMWSA-N Lactose Natural products O([C@@H]1[C@H](O)[C@H](O)[C@H](O)O[C@@H]1CO)[C@H]1[C@@H](O)[C@@H](O)[C@H](O)[C@H](CO)O1 GUBGYTABKSRVRQ-UUNJERMWSA-N 0.000 description 3
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JP2009553600A 2007-03-16 2008-03-10 接着斑キナーゼのインヒビター Expired - Fee Related JP5569956B2 (ja)